M. C. Sheppard

Circulating lipids and minor abnormalities of thyroid function

OBJECTIVE We determined the effect of subclinical hyperthyroidism (defined as low circulating TSH with normal serum free T4) and subclinical hypothyroidism (raised serum TSH with normal free T4) on fasting levels of blood lipids.

Thyroxine replacement therapy and circulating lipid concentrations

OBJECTIVE Hypothyroidism is a common disorder and while the association of overt hypothyroidism with hyper‐cholesterolaemia is clear, the effect upon lipids of the minor abnormalities of thyroid function often found in those receiving T4 replacement therapy is unclear. The aim of the present studies was to define in those with hypothyroidism the effect upon circulating lipids of subtle changes in thyroid status, indicated by serum TSH values below or above the normal range.

Relation between serum interleukin‐6 and thyroid hormone concentrations in 270 hospital in‐patients with non‐thyroidal illness

OBJECTIVESu2003Non‐thyroidal illness (NTI) is frequently accompanied by alterations in circulating thyroid hormone concentrations, despite patients remaining clinically euthyroid. The mechanisms accounting for these changes in circulating thyroid hormone concentrations remain unknown. Much attention has focussed on the role of inflammatory cytokines which are known to be important mediators of disease. The aim of this study was to investigate the role of the cytokine interleukin‐6 (IL‐6) in alterations of thyroid hormone metabolism seen in NTI.

Weight gain following treatment of hyperthyroidism.

OBJECTIVE Patients frequently express concern that treating hyperthyroidism will lead to excessive weight gain. This study aimed to determine the extent of, and risk factors for, weight gain in an unselected group of hyperthyroid patients.

Efficacy of Sandostatin LAR (long-acting somatostatin analogue) is similar in patients with untreated acromegaly and in those previously treated with surgery and/or radiotherapy.

background and objectivesu2002 Somatostatin analogues have been used as an adjunct to surgery and radiotherapy in the treatment of acromegaly for over 15 years, but debate surrounds their use as primary therapy. Newman suggested that octreotide was equally effective as primary or adjuvant therapy, but the effects of previous surgery/radiotherapy may have led to a preselection bias. In an attempt to eliminate this bias, the efficacy of the depot somatostatin analogue Sandostatin® LAR® as primary and adjuvant therapy has been assessed using GH and IGF‐I levels at diagnosis as baseline values.

Cardiovascular function and glucocorticoid replacement in patients with hypopituitarism.

OBJECTIVE Retrospective analysis suggests an increased mortality from cardiovascular disease in hypo‐pituitary adults; GH deficiency has been postulated to account for this. However, glucocorticoid replacement doses of 30 mg/day of hydrocortisone (HC) may be excessive, and could therefore be implicated in the increased cardiovascular mortality in this group of patients. The aims of this study were to establish whether patients with hypopituitarism have any abnormalities of the cardiovascular system compared to a control group and whether any of these parameters might be improved by reducing the replacement dose of glucocorticoid.

SERIAL SERUM THYROGLOBULIN MEASUREMENTS IN THE MANAGEMENT OF DIFFERENTIATED THYROID CARCINOMA

Serum thyreoglobulin (Tg) was measured on repeated occasions in 416 patients with differentiated thyroid cancer for up to 7 years after initial therapy. All patients had thyroidectomy and/or ablative 131I therapy and all measurements were done while patients were receiving T4 replacement. Tg was measured using a double‐antibody radioimmunoassay. Overall correlation between serum Tg concentration and presence or absence of cancer was 95‐9%. At the time of initial measurement 295 patients had serum Tg <5 μg/1, and in the latest analysis only 1‐7% of these patients showed evidence of disease. Initially there were 19 patients of a total of 121 with serum Tg > 5 μg/l in whom no cancer was apparent. In eight of these 19 subjects recurrent or metastatic disease has been diagnosed up to 3‐5 years after the first measurement indicating that in these cases serum Tg values were ‘predictive’. Serum Tg appears to be a sensitive and specific means of detecting residual, recurrent or metastatic thyroid cancer and in most situations can replace routine, expensive and inconvenient radioactive thyroid scans; these should be performed when serum Tg values are elevated or when there is clinical evidence suggesting recurrence.

Prediction of cure and risk of hypothyroidism in patients receiving 131I for hyperthyroidism

Contextu2002 There is little consensus regarding the most appropriate dose of radioiodine (131I) to be administered to patients with hyperthyroidism.

Abnormal expression of 11 beta-hydroxysteroid dehydrogenase type 2 in human pituitary adenomas: a prereceptor determinant of pituitary cell proliferation.

The physiological effects of glucocorticoids (GCs) are, at least in part, mediated by inhibition of cell proliferation. Two isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD) interconvert cortisol (F) and inactive cortisone (E), and are thus able to modulate GC action at an autocrine level. Previously, we have demonstrated absent expression of 11β-HSD2 in normal pituitaries; however, in a small number of pituitary tumors analysed, 11β-HSD2 was readily demonstrable. Here we have used real-time RT–PCR to quantify expression of mRNA for 11 β-HSD1 and 2 in 105 human pituitary tumors and have performed enzyme expression and activity studies in primary pituitary cultures. Overall, pituitary tumors expressed lower levels of 11β-HSDl mRNA compared with normals (0.2-fold, P<0.05). In contrast, expression of 11β-HSD2 mRNA was 9.8-fold greater in tumors than in normals (P<0.001). Enzyme assays showed significant 11β-HSD2 activity (71.9±22.3u2009pmol/h/mg protein (mean±s.d.)) but no detectable 11β-HSDl activity. Proliferation assays showed that addition of glycyrrhetinic acid (an 11β-HSD2 inhibitor) resulted in a 30.3±7.7% inhibition of cell proliferation. In summary, we describe a switch in expression from 11β-HSDl to 11β-HSD2 in neoplastic pituitary tissue. We propose that abnormal expression of 11β-HSD2 acts as a proproliferative prereceptor determinant of pituitary cell growth, and may provide a novel target for future tumor therapy.

Dysregulation of iodothyronine deiodinase enzyme expression and function in human pituitary tumours.

objective Thyroid hormones (THs) perform essential roles in pituitary function. They regulate anterior pituitary hormone secretion and are also key determinants of pituitary cell proliferation and differentiation. The critical role of deiodinase enzymes, which serve as prereceptor regulators of TH action, remains largely unexplored. Three deiodinase enzymes metabolize active and inactive THs and thereby determine tissue concentrations of the biologically active ligand, tri‐iodothyronine (T3). We hypothesized that aberrant expression of deiodinase enzymes and/or altered enzyme activity in pituitary tumours may change tissue concentrations of THs and influence their growth and secretory characteristics.